Acute Graft Versus Host DiseasePhase 3NCT03057054

Lactobacillus Plantarum in Preventing Acute Graft Versus Host Disease in Children Undergoing Donor Stem Cell Transplant

A Phase 3 study testing Allogeneic Hematopoietic Stem Cell Transplantation, Lactobacillus plantarum strain 299 and Lactobacillus plantarum strain 299v in people with Acute Graft Versus Host Disease and Hematopoietic and Lymphatic System Neoplasm, run by Children's Oncology Group at 43 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

This randomized phase III trial studies how well Lactobacillus plantarum works in preventing acute graft versus host disease in children undergoing donor stem cell transplant. Lactobacillus plantarum may help prevent the development of gastrointestinal graft versus host disease in children, adolescents, and young… Read more about this study

Who is it for?: Ages 2 to 25 years
Conditions the study is for: Acute Graft Versus Host Disease, Hematopoietic and Lymphatic System Neoplasm, Leukemia
What is being tested?: Allogeneic Hematopoietic Stem Cell Transplantation, Lactobacillus plantarum strain 299 and Lactobacillus plantarum strain 299v
Type of treatment: Surgery or procedure
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 173 participants
Where: 43 sitesin 2 countries
Study dates: 30 Apr 2018to 30 Jun 2026
Phase: Phase 3

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 2 to 25 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

All clinical and laboratory studies, if applicable, must be obtained within 21 days prior to start of protocol therapy (repeat if necessary); protocol therapy must begin within 6 months of study enrollment
Patient must have a diagnosis that is managed with an alternative donor allogeneic hematopoietic cell transplant
Patients must have a Lansky (for patients =< 16 years of age) or Karnofsky (for patients > 16 years of age) performance status score of >= 70; patients who are unable to walk because of a chronic underlying condition (such as paralysis), but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing performance score
Hematopoietic cell transplant (HCT)
Patient must be receiving cells from alternative donor defined as one of the following:
Unrelated donor with a complete human leukocyte antigen (HLA) match or a 1 or 2 HLA mismatch, considering only HLA-A, HLA-B, HLA-C, and HLA-DRB1
Related donor with a 1 or more HLA mismatch (including haplo-identical)
Note: History of HCT or other cellular therapy (e.g. chimeric antigen receptor [CAR]-T cells, donor lymphocyte infusions) is permitted

Who cannot join

Patient plans on receiving stem cells from a matched (8/8) related donor
Patient has used a probiotic dietary supplement within the previous 30 days of enrollment; (consumption of yogurt products is allowed)
Patient has a history of severe GI tract insult including but not limited to previous bowel perforation, grade 4 neutropenic colitis or typhlitis, inflammatory bowel syndrome, short small bowel syndrome (Crohn's disease, ulcerative colitis), history of gastrointestinal GVHD, or history of bowel resection
Patient has a medical, psychiatric or social issue that would compromise patient safety or compliance with protocol therapy, or interfere with consent, study participation, follow up, or interpretation of study results
Female patients who are pregnant are not eligible; women of childbearing potential require a negative pregnancy test prior to enrollment
Patient has diarrhea at the time of enrollment which is Clostridium difficile toxin positive
Patient is receiving antibiotic therapy for an active bacterial infection
Patient is allergic to all third or fourth generation cephalosporins, carbapenems, and all aminoglycosides, which are used to empirically treat LBP bacteremia

Trial locations and contacts

43 sites in 2 countries.

Country

City, postcode or hospital

43 sites in 2 countries

United States40 sites

C S Mott Children's Hospital
Ann Arbor, Michigan, 48109
Children's Hospital Colorado
Aurora, Colorado, 80045
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Children's Hospital of Alabama
Birmingham, Alabama, 35233
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Roswell Park Cancer Institute
Buffalo, New York, 14263
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Nationwide Children's Hospital
Columbus, Ohio, 43205
Medical City Dallas Hospital
Dallas, Texas, 75230
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
University of Florida Health Science Center - Gainesville
Gainesville, Florida, 32610
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96826
Riley Hospital for Children
Indianapolis, Indiana, 46202
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108
Children's Hospital Los Angeles
Los Angeles, California, 90027
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
The Children's Hospital at TriStar Centennial
Nashville, Tennessee, 37203
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
Yale University
New Haven, Connecticut, 06520
Children's Hospital New Orleans
New Orleans, Louisiana, 70118
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Nemours Children's Hospital
Orlando, Florida, 32827
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Oregon Health and Science University
Portland, Oregon, 97239
University of Rochester
Rochester, New York, 14642
Children's Hospital of San Antonio
San Antonio, Texas, 78207
Methodist Children's Hospital of South Texas
San Antonio, Texas, 78229
Rady Children's Hospital - San Diego
San Diego, California, 92123
UCSF Medical Center-Mission Bay
San Francisco, California, 94158
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701
New York Medical College
Valhalla, New York, 10595
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803

Other trials in United States

Canada3 sites

Alberta Children's Hospital
Calgary, Alberta, T3B 6A8
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5
Hospital for Sick Children
Toronto, Ontario, M5G 1X8

Other trials in Canada

About this study

Official title: The Effectiveness of Lactobacillus Plantarum (LBP, IND# 17339) in Preventing Acute Graft-Versus-Host Disease (GvHD) in Children Undergoing Alternative Hematopoietic Progenitor Cell Transplantation (HCT)

Read the detailed description

PRIMARY OBJECTIVE:

To determine efficacy of orally-administered Lactobacillus plantarum (LBP) in preventing the development of gastrointestinal (GI) acute graft versus host disease (aGvHD) in children and adolescents undergoing alternative donor allogeneic hematopoietic cell transplantation (alloHCT).

EXPLORATORY OBJECTIVES:

To determine whether orally-administered LBP decreases the incidence of grade II-IV aGvHD following alternative donor alloHCT.

II. To determine whether LBP administration maintains intestinal integrity as measured by mean serum citrulline levels and reduction in mucosal barrier injury (MBI) bacteremia.

III. To measure the effects of LBP on the intestinal flora phylogenetic composition during and after alternative donor alloHCT using 16S ribosomal ribonucleic acid (rRNA) gene deep sequencing.

IV. To measure effects of LBP on intestinal flora function during and after alternative donor alloHCT using metagenomic and metabolite profiling.

To measure proposed immunomodulatory effects of LBP in mean serum levels of alloreactive-induced inflammatory cytokines (IL-2, IL-6, IL-12p70, IFN gamma, TNF alpha, etc) in patients receiving LBP compared to placebo.

VI. To determine whether LBP administration reduces the incidence of Clostridium difficile-associated diarrhea in alternative donor HCT patients.

VII. To determine whether LBP administration reduces hospital days within the first 120 days post hematopoietic cell transplant (HCT).

VIII. To define the safety of orally administered LBP strains 299 and 299v in alternative donor HCT patients as measured by incidence of Lactobacillus plantarum bacteremia.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive Lactobacillus plantarum strains 299 and 299v orally (PO) or through nasojejunal (NJ), nasogastric (NG) or gastronomy (G) tube once daily (QD) on day 1 of transplant conditioning regimen to 56 days post alloHCT. Patients undergo alloHCT at day 0.

ARM II: Patients receive placebo PO or through NJ, NG or G tube QD on day 1 of transplant conditioning regimen to 56 days post alloHCT. Patients undergo alloHCT at day 0.

After completion of study treatment, patients are followed up for 120 days from alloHCT.

Conditions: Acute Graft Versus Host Disease, Hematopoietic and Lymphatic System Neoplasm, Leukemia, Lymphoma
Being tested: Allogeneic Hematopoietic Stem Cell Transplantation, Lactobacillus plantarum strain 299, Lactobacillus plantarum strain 299v, Placebo Administration
Medical subject headings: Leukemia, Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery
Also called Allogeneic, Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC
Undergo alloHCT
Lactobacillus plantarum strain 299Biological
Also called DSM 6595, LACTOBACILLUS PLANTARUM 299
Given PO or via NJ, NG or G tube
Lactobacillus plantarum strain 299vBiological
Also called DSM 9843, LACTIPLANTIBACILLUS PLANTARUM 299V, Lp 299v
Given PO or via NJ, NG or G tube
Placebo AdministrationOther
Given PO or via NJ, NG or G tube

Study groups in NCT03057054
Study group	Role	What they receive
Arm I (Lactobacillus plantarum, alloHCT)	Experimental	Patients receive Lactobacillus plantarum strains 299 and 299v PO or through NJ, NG or G tube QD on day 1 of transplant conditioning regimen to 56 days post alloHCT. Patients undergo alloHCT at day 0. Receives: Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Biological: Lactobacillus plantarum strain 299; Biological: Lactobacillus plantarum strain 299v
Arm II (placebo, alloHCT)	Placebo comparator	Patients receive placebo PO or through NJ, NG or G tube QD on day 1 of transplant conditioning regimen to 56 days post alloHCT. Patients undergo alloHCT at day 0. Receives: Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Other: Placebo Administration

What is being measured

The primary outcome is the main question the study is designed to answer.

Proportion of Participants With Stage 1-4 Gastrointestinal (GI) Acute Graft Versus Host Disease (aGVHD)
The proportion of eligible patients having stage 1-4 GI aGvHD occur from Day 0 through Day 120 will be compared between the two arms.
Measured: Up to 120 days post stem cell infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Apr 201830 Jun 2026

First posted17 Feb 2017
Study start30 Apr 2018
Primary completion30 Jun 2022
Study completion30 Jun 2026 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Acute Graft Versus Host DiseaseStudies of the same condition, open and under way.
More trials run by Children's Oncology GroupThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 173 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03057054
Sponsor's protocol ID: ACCL1633
Other IDs: NCI-2017-00208, ACCL1633, COG-ACCL1633, ACCL1633, R01CA201788, UG1CA189955
Status last verified: Sep 2025
First submitted: 15 Feb 2017
Last updated: 6 Oct 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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